Patent Docs

The "Ending the Diagnostic Odyssey Act of 2019"

By Kevin E. Noonan --

On January 6, 2020, a bi-partisan coalition of Senators, including Senator Collins (R-ME), Doug Jones (D-AL), Martha McSally (R-AZ), and Bob Menendez (D-NJ), introduced the "Ending the Diagnostic Odyssey Act of 2019" to permit states to use Medicaid funding for whole genome sequencing (WGS) analysis in children having certain rate diseases.  The bill is a counterpart of H.R. 4144, introduced by Rep. Scott Peters (CA-52), joined by Rep. Shimkus and Mr. Vargas, on August 2, 2019.

The stated purpose of the bill is "[t]o enable States to better provide access to whole genome sequencing clinical services for certain undiagnosed children under the Medicaid program" and, of course, "for other purposes."  The bill purports to effectuate this legislative purpose by providing the States with an option to expressly achieve the stated objective.  This is to be done by amending Title XIX of the Social Security Act, codified at 42 U.S.C. ch.7, by inserting new section 1947, which states in pertinent part:

[A] State, at its option as a State plan amendment, may provide for medical assistance under this title to an eligible individual for purposes of providing the individual with whole genome sequencing clinical services.  Sec. 1947 (a)

Section (b) provides authorization for the state to pay a "health care provider" for WGS to an "eligible individual" (defined later in the bill as individuals who are "eligible for medical assistance under the State plan (or a waiver of such plan)" and are under 21 (or 20, 19, or 18 "as the state may choose" and has been "referred or admitted to an intensive care unit, or has been seen by at least 1 medical specialist, for a suspected genetic or undiagnosed disease; or is suspected by at least 1 medical specialist to have a neonatal- or pediatric- onset genetic disease") (Section 1947(f(1)).  During the first 12 fiscal year quarters (i.e., the first three fiscal years), the Federal percentage applicable to these payments would only provide 75% of the costs.  Part of the Federal support for this program includes planning grants (which shall also require a percentage of State matching funds as determined under section 1905(b) of the statute), and the State plan must establish procedures for referring any eligible individual to a health care provider qualified to provide WGS services (Sec. 1947(c)).

The bill also contains requirements for the States (Section 1947(d)) to provide within three years of initiation a program under these provisions of the Act reports to the Administrator of the Centers for Medicare & Medicaid Services and the Administrator of the Health Resources and Services Administration on the extent to which these service "reduce health disparities" (presumably disparities existing between those who can and those who cannot afford WGS services under existing law) and the converse, "the extent to which coverage under the State plan (or a waiver of such plan) impedes the use of genetic and genomic testing that may improve clinical outcomes for eligible individuals enrolled in the State plan (or under a waiver of such plan).  Health care providers (Section 1947(e)) must report to the State "on all applicable measures for determining the quality of such service."  Finally, "whole genome sequencing" is expressly defined as:

[T]he unbiased sequencing of all deoxyribonucleic acid bases in the genome of such individual and, if for the sole benefit of the individual, a biological parent of such individual for the purpose of determining whether one or more potentially disease-causing genetic variants are present in the genome of such individual or such biological parent; and . . . includes any analysis, interpretation, and data report derived from such sequencing.''  (Section 1947(f)(2)).

Senator Collins's Homepage defines the "genetic odyssey" in the bill's title as the delay children with rare genetic diseases endure, which the Senator says last 5-7 years on average.  The tragedy of this odyssey is that many of these children do not live more than 5 years, making the provisions of the bill a life-and-death proposition for them.  According to the website, "[t]here are approximately 7,000 rare diseases known today; approximately 80 percent of rare diseases are genetic, and about one-half of all rare diseases affect children."  The Senator asserts that her bill is supported by over 100 patient advocacy groups, including "the Genetic Alliance, the Parent Project Muscular Dystrophy, Tuberous Sclerosis Alliance, Alström Syndrome International, Epilepsy Foundation, and the Asthma and Allergy Foundation of America."

The bill is expected to be taken up in due course; H.R. 4144 has been referred to the House Committee on Energy and Commerce but the committee has taken no further action since August.

CRISPR Interference Update

By Kevin E. Noonan --

All interferences have filings that are either kept confidential or are entirely procedural in nature.  While there is little substantive to discuss, acknowledging them serves the purpose of keeping track of the proceedings; the following papers have been filed in Interference No 106,115 between Senior Party The Broad Institute, Harvard University, and the Massachusetts Institute of Technology, and Junior Party the University of California, Berkeley, the University of Vienna, and Emmanuelle Charpentier (collectively, "CVC") over patents and applications that disclose and claim eukaryotic cell-embodiments of CRISPR technology:

CVC Protective Order Entered -- December 9, 2019
Broad Notice of Filing Priority Statement -- December 12, 2019
CVC Notice of Filing Priority Statement -- December 12, 2019
Deposition Notice Randall Peterson Ph.D. -- December 12, 2019
Broad Priority Statement Filing -- December 12, 2019
CVC Priority Statement Filing -- December 12, 2019
Broad Notice of Priority Statement Service -- December 13, 2019
CVC Notice of Priority Statement Service -- December 13, 2019
CVC Fourth Updated Notice of Related Proceedings -- December 23, 2019

Dr. Peterson's deposition was scheduled to take place on December 17th and 18th, pursuant to the schedule set forth by the Board's Order (see "CRISPR Housekeeping").

Finally, for now, on December 23rd, CVC provided an updated Notice of Related Proceedings, informing the Board and the Broad of the following newly granted patents (as well as additional pending applications), none of which are involved in this interference:

10,301,651 (USSN 14/685,504); 10,227,611 (USSN 14/042,782); 10,407,697 (USSN 15/435,233); 10,385,360 (USSN 15/925,544); 10,421,980 (USSN 16/033,002); 10,415,061 (USSN 16/033,005); 10,308,961 (USSN 16/033,016); 10,358,658 (USSN 16/201,836); 10,337,029 (USSN 16/201,848); 10,351,878 (USSN 16/201,855); 10,400,253 (USSN 16/276,343); 10,428,352 (USSN 16/276,348); 10,443,076 (USSN 16/276,356); 10,487,341 (USSN 16/277,090); 10,519,467 (USSN 15/803,424); 10,526,619 (USSN 16/380,758); and 10,513,712 (USSN 16/382,093); allowance of USSN 16/380,781; allowance of USSN 16/382,096; allowance of USSN 16/382,097; and allowance of USSN 16/382,100.

Season's Greetings from Patent Docs

The authors and contributors of Patent Docs wish their readers and families a Happy Holidays!  Publication of Patent Docs will resume on December 26th.

The authors and contributors of Patent Docs wish their readers and families a Happy Holidays!  Publication of Patent Docs will resume on December 26th.

Broad Files Reply Brief to Berkeley's Opposition to Substantive Motion No. 1

By Kevin E. Noonan --

In early November, Senior Party the Broad Institute (along with Harvard University and the Massachusetts Institute of Technology) filed their response to Junior Party the University of California/Berkeley, the University of Vienna, and Emmanuelle Charpentier (collectively, "CVC") Opposition to the Broad's Substantive Motion No. 1 in Interference No. 105,166.

Pursuant to the Patent Trial and Appeal Board's rules, the Broad's Reply Brief follows formulaically with Senior Party's point-by-point rebuttal of CVC's grounds for opposition.  CVC's first asserted opposition argument was that "judgment estoppel" (quotation marks in opposition brief) does not exist in any form that would prelude this interference.  The Broad characterizes this argument as "remarkable," and that it "not only displays a lack of understanding regarding the development of the estoppel rule in interferences, but it also misstates common law estoppel principles."  Segueing to the question of "motion estoppel" under Rule 41.127(a), the Broad traces the provisions of this Rule to former Rule 1.658(c), which provided (according to the Broad) for "broad application of estoppel for any type of interference judgment and further listed specific motions that needed to be raised lest motion estoppel apply, including failure to move to add a new claim" (which the Broad argues is the case here).  These considerations did not change with revision of the interference rules, according to the Reply Brief, and thus the Board remains empowered under the rules to grant its motion that CVC should be estopped in this interference by the Board's judgment in the prior interference (No. 105,048).

The brief next argues that Rule 127 applies to judgments of no interference-in-fact, contrary to CVC's argument that it cannot because there is no "losing" party under those circumstances, on the basis that there is no express provision in the Rule to this effect.  According to the Broad, "the first sentence sets out a general rule, while the second sentence applies it to losing parties and sets out an exception for losing parties"; this does not negate application of estoppel to CVC under the circumstances of this interference, according to the Broad.

The Broad takes direct issue with CVC's argument that the PTAB is powerless to apply estoppel here because doing so would be contrary to "common law estoppel principles," saying bluntly (with reference to Wright's Federal Practice and Procedure treatise) that CVC "misapprehends fundamental principles of claim and issue preclusion," specifically that common law estoppel "foreclos[e] any litigation of matters that never have been litigated, because of a determination that they should have been advanced in an earlier suit."  This argument also supports the Broad's rebuttal that 35 U.S.C. § 135(a) "mandates that the PTAB resolve any and all potential priority issues," saying that "the Federal Circuit rejected this argument long ago" citing Eli Lilly & Co. v. Bd. of Regents of Univ. of Washington, 334 F.3d 1264, 1267 (Fed. Cir. 2003).  According to the Broad, "[t]he PTAB thus has the discretion and authority to promulgate rules for discontinuing interferences, including estoppel rules that provide consequences for a party's failure to make timely motions."

The brief then reiterates its argument that CVC had the opportunity (to which it did not avail itself) to add a claim to eukaryotic cell embodiments of CRISPR technology in the '048 Interference (pointing out that CVC had indicated in that prior interference that it "might seek authorization to file such a responsive motion").  Having failed to prevail in that interference the Broad characterizes CVC's position in this interference as attempting to get a "second bite at the apple" that the estoppel rules preclude.  Further, the Broad disputes CVC's argument that it "could not have moved to add a eukaryotic claim in the '048 Interference because it had no allowed eukaryotic claims at that time," asserting that Standing Order ¶ 208.5.1 permits this.  And the Broad rejects CVC's assertion that the Broad could have moved just as well, because Standing Order ¶ 208.5.1 requires the moving party to certify that such a claim was patentable to CVC, which the Broad could not (and certainly would not) do.

Finally in this portion of the brief, the Broad challenges CVC's argument that the "the alleged separate patentability of single-molecule RNA claims" over the Count in the '048 Interference raises a factual issue that precludes the Board from granting the Broad's Substantive Motion No. 1.  Here, the Broad argues that this argument is "legally irrelevant," because CVC had the opportunity to file claims to interfering subject matter (i.e., "eukaryotic claims limited to use of single-molecule RNA") but did not.

Returning to the issue of "judgment estoppel," the brief cites MPEP § 2308(b) for the proposition that such estoppel "bars a second interference as to 'claims to the same invention as the count of the interference.'"  That is the case here, because "the Broad's single-molecule RNA claims were designated as corresponding to the prior Count," a designation never challenged by CVC.

The brief then sets forth detailed arguments for each of its propositions regarding why CVC's Opposition fails to rebut its arguments in support of Substantive Motion No. 1.  To CVC's argument that Rule 127 estoppel does not apply to judgments of no interference-in-fact, the Broad argues that CVC's argument "conflicts with the language of the first sentence and does not give application to both sentences."  The first sentence of the Rule, the Broad argues, sets out estoppel without regard to "winners" and "losers," while the second sentence is directed at the "losing" party and setting forth an exception for "any contested subject matter for which that party was awarded a favorable judgment."  In the Broad's calculus, neither of these provisions provides CVC with the benefit of pursuing this interference after having failed to pursue subject matter relating to eukaryotic cell embodiments of CRISPR in the '048 Interference.  The Broad further cites the Notice of Proposed Rulemaking for Rule 127, 68 Fed. Reg. 66648, 66661 (Nov. 26, 2003), which they argue "flatly contradict[s]" CVC's interpretation of the Rule, and further notes that CVC's argument amounts to an admission that Rule 127 applies to situations where the Board finds there to be no interference-in-fact.  Finally on this point the Broad disputes CVC's characterization of the Board's finding of no interference-in-fact as being merely jurisdictional and amounting to dismissal; in their view the Board entered judgment and thus that decisions provokes the estoppel effects set forth in Rule 127.

The brief then sets out an exposition of the Broad's understanding and assertion of the development of the PTAB's estoppel rules, going into detail regarding the similarities and differences between Rule 1.658(c) and Rule 127.  In brief, the Broad argues that Rule 1.658(c) applied to "any type of judgment" and that revision of the Rule did not change (and was not intended to change) the scope of this estoppel.  And here the brief revisits a familiar refrain, asserting that under Rule 1.658(c) the estoppel would apply for a party that failed to file a motion to add a claim regardless of whether judgment was entered on priority or "ancillary grounds," meaning in this case a finding of no interference-in-fact.

The Broad also argues that these estoppel rules promulgated by the PTAB are not inconsistent with common law principles.  Citing Nevada v. United States, 463 U.S. 110, 129-30 (1983), they argue that "common law principles recognize that final judgment in an action results in estoppel with respect to undecided issues that could have been raised but were not" (and further assert that the case CVC cited in support of its position, Duvall v. Atty. Gen. of U.S., 436 F.3d 382, 388 (3d Cir. 2006), is in fact consistent with the Broad's own analysis of estoppel principles in the interference context.

Next, the Broad maintains that there is no statutory requirement that the PTAB always determine priority, based in the Board's discretion whether to declare an interference in the first place (although this argument does not reach the question of whether such a requirement arises once the PTO properly institutes an interference proceeding, although the brief does cite the Director's discretion (but surely not unfettered) to discontinue an interference).

The brief then turns to a disquisition on why CVC's arguments are merely "post-hoc" attempts to be absolved from its failure to move to add eukaryotic CRISPR claims in the '048 Interference.  (Indeed, the entirety of the Broad's argument boils down to this point.)  The Broad rebuts CVC's contention that its claims were not in condition for allowance as a rationale (amounting to essentially a ripeness argument), based on the absence of any such requirement in Standing Order ¶ 208.5.1 (albeit being an argument of inference rather than directly stated).  The Broad further characterizes CVC's arguments as improperly attempting to blame the PTAB for its failure to move, citing colloquy from the teleconference between the parties and the Board regarding authorization to file motions.  The Broad states frankly that CVC's argument that the Broad was required to add a claim directed to eukaryotic CRISPR to CVC's application in the '048 Interference was wrong, because Standing Order ¶ 208.5.1 would have required the Broad to "[c]ertify that the movant is not aware of any reason why the claim is not patentable," which they certainly were not willing to do.  The brief points out the inconsistency in CVC's arguments regarding prosecution strategy in view of CVC having previously presented eukaryotic CRISPR claims before (and then cancelling them) suggesting the '048 Interference.  Finally, the Broad (in a more semantical than legal argument) attempts to rebut CVC's argument that it had not provoked an interference in this case, because by copying the Broad's claims it did so (as opposed to suggesting an interference), which CVC certainly did not do.

The brief ends with two points.  First, that this interference is estopped in totality (in opposition to CVC's argument that the scope of any estoppel is limited to dual-molecule CRISPR embodiments), addressing both motion estoppel and judgment estoppel, and restating succinctly its argument in favor of estoppel:

The PTAB's rules afforded CVC every opportunity to present claims and arguments regarding the eukaryotic subject matter of the 048 Interference.  The PTAB's rules do not allow a second run at another party's claims to that same subject matter in a later interference.  Indeed, allowing otherwise would vitiate the goals of finality and efficiency served by the estoppel rules.

And of course the Broad does not miss its opportunity to state unequivocally that "CVC's claims should not issue" in the event that this interference should be dissolved based on the Broad's own arguments about estoppel:

CVC's argument ignores that Broad has already been awarded claims to the eukaryotic invention in issued patents.  CVC cannot obtain claims to the same subject matter absent an interference with Broad.  CVC could have had such an interference previously but strategically declined to give the PTAB the option of implementing such an interference at that time.  Accordingly, CVC is estopped from pursuing such an interference, and cannot obtain Broad's eukaryotic claims.

Berkeley Files Responsive Motion to Broad's Substantive Motion No. 2 in Interference

By Kevin E. Noonan --

As previously discussed, Senior Party The Broad Institute (joined by Harvard University and MIT) on October 14th filed Substantive Motion No 2 (to substitute the count) in the current interference over CRISPR technology (No. 106,115).

Count 1 of the interference as declared is:

An engineered, programmable, non-naturally occurring Type II CRISPR-Cas system comprising a Cas9 protein and at least one guide RNA that targets and hybridizes to a target sequence of a DNA molecule in a eukaryotic cell, wherein the DNA molecule encodes and the eukaryotic cell expresses at least one gene product and the Cas9 protein cleaves the DNA molecules, whereby expression of the at least one gene product is altered; and, wherein the Cas9 protein and the guide RNA do not naturally occur together, wherein the guide RNAs comprise a guide sequence fused to a tracr sequence.

or

A eukaryotic cell comprising a target DNA molecule and an engineered and/or non-naturally occurring Type II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-— CRISPR associated (Cas) (CRISPR-Cas) system comprising
    a) a Cas9 protein, or a nucleic acid comprising a nucleotide sequence encoding said Cas9 protein; and
    b) a single molecule DNA-targeting RNA, or a nucleic acid comprising a nucleotide sequence encoding said single molecule DNA-targeting RNA; wherein the single molecule DNA-targeting RNA comprises:
        i) a targeter-RNA that is capable of hybridizing with a target sequence in the target DNA molecule, and
        ii) an activator-RNA that is capable of hybridizing with the targeter-RNA to form a double-stranded RNA duplex of a protein- binding segment,
    wherein the activator-RNA and the targeter-RNA are covalently linked to one another with intervening nucleotides; and
    wherein the single molecule DNA-targeting RNA is capable of forming a complex with the Cas9 protein, thereby targeting the Cas9 protein to the target DNA molecule, whereby said system is capable of cleaving or editing the target DNA molecule or modulating transcription of at least one gene encoded by the target DNA molecule.

The Broad's proposed Count 2 is:

A method, in a eukaryotic cell, of cleaving or editing a target DNA molecule or modulating transcription of at least one gene encoded by the target DNA molecule, the method comprising:
    contacting, in a eukaryotic cell, a target DNA molecule having a target sequence with an engineered and/or non-naturally-occurring Type II Clustered Regularly lnterspaced Short Palindromic Repeats (CRISPR)-CRISPR associated Cas) (CRISPR-Cas) system comprising:
        a) a Cas9 protein, and
        b) RNA comprising
            i) a targeter-RNA that is capable of hybridizing with the target sequence of the DNA molecule or a first RNA comprising (A) a first sequence capable of hybridizing with the target sequence of the DNA molecule and (B) a second sequence; and
            ii) an activator-RNA that is capable of hybridizing to the targeter-RNA to form an RNA duplex in the eukaryotic cell or a second RNA comprising a tracr sequence that is capable of hybridizing to the second sequence to form an RNA duplex in the eukaryotic cell,
    wherein, in the eukaryotic cell, the targeter-RNA or the first sequence directs the Cas9 protein to the target sequence and the DNA molecule is cleaved or edited or at least one product of the DNA molecule is altered.

The distinction the Broad made in its Motion is between embodiments of CRISPR methods that are limited to "single-molecule guide RNA" (aka "fused" or "covalently linked" species), versus embodiments that encompass single-molecule and "dual molecule" species (wherein the in the latter versions the "targeter-RNA" and "activator-RNA" as recited in the proposed Count are not covalently linked).  The Broad argued that this Count should be adopted by the Board because it "properly describes the full scope of the interfering subject matter between the parties because both parties have involved claims that are generic, non-limited RNA claims."  The brief also argued that proposed Count 2 "sets the correct scope of admissible proofs [i.e., their own] for the breakthrough invention described by the generic claims at issue in these proceedings—the successful adaption of CRISPR-Cas9 systems for use in eukaryotic environments," which The Broad contended current Court 1 (in either alternative) does not.

Early last month (November 7th), Junior Party the University of California, Berkeley; the University of Vienna; and Emmanuelle Charpentier; collectively, "CVC") filed its Responsive Motion (Contingent) to the Broad's motion no. 2, to be awarded priority to its earlier applications for the subject matter of proposed new Count 2.  (Careful readers with appreciate that in many ways this brief is substantially identical to CVC's Substantive Motion No. 1 filed to be accorded benefit to the same priority applications for the current Count.)  As required by the rather formulaic procedural rules of interferences, the brief is structured to address (and rebut) Senior Party's argument; the argument (simply stated) is that CVC is entitled to priority to the following priority applications: USSN 61/652,086, filed May 25, 2012 (P1); USSN 61/716,256, filed October 19, 2012 (P2): USSN 61/757,640, filed January 28, 2013 (P3);    USSN 13/842,859, filed March 15, 2013; USSN 14/685,504, filed April 13, 2015; or USSN 15/138,604, filed April 26, 2016.

Mirroring the Broad's motion, CVC sets forth in detail the disclosure in its earlier priority applications for at least one embodiment falling within the scope of proposed Count 2.  And as the Broad did in its motion, the brief hagiograhically recites the "ground-breaking" nature of their work, stating that the earliest priority document (P1) disclosed "the minimal components required to generate a functional CRISPR-Cas9 DNA-cleavage complex—Cas9, crRNA, and tracrRNA."  In addition, and addressing the Broad's argument that CVC's disclosure (and this interference) were directed to single-molecule embodiments of CRISPR, CVC argues that on the contrary this priority document "disclosed, for the first time, that complexes of Cas9 and a double- or single-molecule DNA-targeting RNA . . . are useful for targeted DNA cleavage and described numerous applications of this gene-editing technology, including modifying target DNA in eukaryotic cells" and that "[t]he CVC inventors immediately understood that the CRISPR-Cas9 DNA-cleavage complex could be used in a variety of different cellular and noncellular settings."  The brief recites (prophetic) Example 1 in the P1 specification, asserting that the failure of the P1 specification to show actual reduction to practice is not required to satisfy the requirement for entitlement benefit.  CVC also cautions the Board against any attempt by the Broad to "erroneously to link the issues in this motion to the PTAB's termination of Interference No. 106,048 due to no interference-in-fact," stating that "the legal and factual issues raised here are fundamentally different from those decided in the prior '048 proceeding" based on the PTAB's own prior statements of the grounds for its no interference-in-fact determination. Rather, according to CVC:

[A person of ordinary skill in the art] reading P1 in light of the state of the art at the time of filing would have understood that the application describes and enables at least one embodiment within the scope of Proposed Count 2.  Moreover, post-filing-date publications report successfully practicing CVC's claimed invention in eukaryotes using the very methods and components that P1 describes.  The Board should therefore accord CVC the benefit of P1's May 25, 2012 filing date with respect to Proposed Count 2.

What follows is a succinct statement of the Precise Relief Requests (pursuant to PTAB rules) and support in the P1 specification for this relief, recited in the alternative with the other priority documents recited in CVC's request for relief.  The standard, undisputed by the parties, is that to be accorded benefit of priority a prior application must show constructive reduction to practice (CRTP) regarding at least one embodiment falling within the scope of the count, citing Falkner v. Inglis, 448 F.3d 1357, 1362 (Fed. Cir. 2006).  After setting out the legal grounds for CRTP, the brief then applies these rubrics to the disclosure in P1 for subject matter falling within the scope of Count 2 (which CVC argues satisfies these requirements).  Along the way, the brief also suggests that "Broad will doubtlessly rely on cherry-picked quotes about whether or not the inventors or experts knew CRISPR would work in eukaryotic cells before testing it," rejecting these anticipated arguments on the ground that CTRP is grounded on what is disclosed in the specification.  The relevant P1 disclosure for CVC is that CRISPR is functional "when removed from its natural prokaryotic cellular milieu, which is highly relevant here because it establishes CVC's possession of the necessary and sufficient components for a functional CRISPR-Cas9 DNA-cleavage complex regardless of its environment" (emphasis in brief).

The argument is illustrated by Figures from the P1 application:

And explicit disclosure compared with the elements of proposed Count 2.

The brief then sets forth specific disclosure related to the elements of Count 2 (also provided in Appendix 3 entitled "Exemplary Evidence of Constructive Reduction to Practice of Proposed Count 2 in the P1 '068 Application"), and CVC further asserts that "[t]he inventors fully grasped the broad utility of such a method as aptly illustrated by the many types of 'target cells of interest' suitable for the methods described in P1, including a variety of eukaryotic cells (elements [1]-[2]) such as a fish, human, and fruit fly cell," noting that "[t]hese features are not merely recited in P1, but diagrammed, discussed, and specifically exemplified showing the inventors' possession" based on express disclosure cited with particularity in the brief (including specifically the prophetic use of CRISPR in fish cells).  CVC presents explicit argument relating to what the skilled worker would understand CVC possessed and would be able to accomplish without undue experimentation with regard to the CRTP requirement for being accorded benefit.  Finally in this regard, the brief asserts that post-filing evidence (much of it by third parties) further supports a conclusion of constructive reduction to practice in the P1 disclosure:

Within a year of CVC publishing that Cas9 and a [single guide RNA] such as chimera A (or a double-molecule RNA) formed a functional DNA-cleavage complex (Ex. 3202), other researchers used materially the same components and methods disclosed in P1 to practice the fish cell embodiment—objectively confirming that P1 enables practicing the method of E4.  While the studies described below published after P1's May 25, 2012 filing

date, post-priority date evidence "may show, for example, that practicing the invention did not require undue experimentation," citing Amgen, Inc. v. Sanofi, 872 F.3d 1367, 1379 (Fed. Cir. 2017); see also, In re Wands, 858 F.2d 731, 739 (Fed. Cir. 1988); In re Hogan, 559 F.2d 595, 605 (Fed. Cir. 1977).

CVC supports its allegations of what the skilled person would understand from the disclosure in the P1 specification by declaration testimony an expert, Dr. Peterson (who eventually will be subject to cross-examination by the Broad in this interference).  Specifically, Dr. Peterson attests extensively to the applicability of CRISPR as set forth in P1 to use in human cells, which CVC asserts is also shown by third-party success in applying CRISPR to human cells, and fruit fly cells.  Thus, CVC asserts "[i]n sum, the great weight of evidence compels a finding that P1 describes and enables each of the fish (E4), human (E5), and fruit fly (E6) cell methods, any one of which, on its own provides a CRTP of Proposed Count 2."

The brief then turns on the distinction between what was required for the Broad to prevail (as it did) in the earlier interference and in this one:

Broad's previously asserted arguments wrongly impose a reasonable expectation of success standard (obviousness) on §112, first paragraph, which contains no such standard.  Obviousness "turns on . . . whether the claimed invention would have been obvious in view of the prior art."  Allergan, Inc. v. Sandoz, Inc., 796 F.3d 1293, 1310 (Fed. Cir. 2015) (emphasis in original).  "In contrast, the enablement inquiry turns on whether the skilled artisan, after reading the specification, would be able to make and use the claimed invention without undue experimentation."  Id. (emphasis in original).  Similarly, "[t]he standard for satisfying the written description requirement is whether the disclosure 'allow(s) one skilled in the art to visualize or recognize the identity of the subject matter purportedly described.'"  Alcon, 745 F.3d at 1190 (emphasis added; citation omitted); see also, Ariad, 598 F.3d at 1351.  Any argument to the contrary erroneously conflates obviousness with written description and enablement.

Finally, the brief argues in the alternative that the other applications CVC asserts for priority contain the P1 disclosure relied upon for priority in this brief, and thus for the same reasons (set forth in brief for each reference) CVC is entitled to priority to these applications, based on the "continuous chain" of priority in these CVC applications.

Berkeley Files Substantive Motion No. 2 to be Accorded Benefit to Earlier Priority Application in Interference

By Kevin E. Noonan --

On October 14th, Junior Party the University of California, Berkeley; the University of Vienna; and Emmanuelle Charpentier; collectively, "CVC") filed its Substantive Motion No. 1 to be awarded priority benefit to their earlier priority applications: USSN 61/652,086, filed May 25, 2012 (P1); USSN 61/716,256, filed October 19, 2012 (P2); USSN 61/757,640, filed January 28, 2013 (P3); USSN 13/842,859, filed March 15, 2013; USSN 14/685,504, filed April 13, 2015; or USSN 15/138,604, filed April 26, 2016, in Interference No. 106,115 against Senior Party the Broad Institute, Harvard University, and the Massachusetts Institute of Technology.

CVC sets forth in detail the disclosure in its earlier priority applications for at least one embodiment falling within the scope of Count 1 of this interference.  The brief recites the "ground-breaking" nature of their work, stating that the earliest priority document (P1) disclosed "the minimal components required to generate a functional CRISPR-Cas9 DNA-cleavage complex—Cas9, crRNA, and tracrRNA."  In addition, CVC argues that this priority document "disclosed, for the first time, that complexes of Cas9 and a double- or single-molecule DNA-targeting RNA . . . are useful for targeted DNA cleavage and described numerous applications of this gene-editing technology, including modifying target DNA in eukaryotic cells," noting the many accolades bestowed upon CVC's inventors by the scientific community.  CVC further argues that "[t]he CVC inventors immediately understood that the CRISPR-Cas9 DNA-cleavage complex could be used in a variety of different cellular and noncellular settings."  The brief recites (prophetic) Example 1 in the P1 specification, and the (albeit prophetic) application of CRISPR technology to fish, human, and fruit fly cells.

The brief is careful to note that any failure of the P1 specification to show actual reduction to practice is not required to satisfy the requirement for entitlement benefit.  CVC also cautions the Board against any attempt by the Broad to "erroneously to link the issues in this motion to the PTAB's termination of Interference No. 106,048 due to no interference-in-fact," stating that "the legal and factual issues raised here are fundamentally different from those decided in the prior '048 proceeding" based on the PTAB's own prior statements of the grounds for its no interference-in-fact determination.  Rather, according to CVC:

[A person of ordinary skill in the art] reading P1 in light of the state of the art at the time of filing would have understood that the application describes and enables at least one embodiment within the scope of the count.  Moreover, post-filing-date publications report successfully practicing CVC's claimed invention in eukaryotes using the very methods and components that P1 describes.  The Board should therefore accord CVC the benefit of its first provisional application.

What follows is a succinct statement of the Precise Relief Requests (pursuant to PTAB rules) and support in the P1 specification for this relief, recited in the alternative with the other priority documents recited in CVC's request for relief.  The standard, undisputed by the parties, is that to be accorded benefit of priority a prior application must show constructive reduction to practice (CRTP) regarding at least one embodiment falling within the scope of the count, citing Falkner v. Inglis, 448 F.3d 1357, 1362 (Fed. Cir. 2006).  After setting out the legal grounds for CRTP, the brief then applies these rubrics to the disclosure in P1 for subject matter falling within the scope of the interference Count (which CVC argues satisfies these requirements).  Along the way the brief also suggests that "Broad will doubtlessly rely on cherry-picked quotes about whether or not the inventors or experts knew CRISPR would work in eukaryotic cells before testing it," rejecting these anticipated arguments on the ground that CTRP is grounded on what is disclosed in the specification citing Ariad Pharms., Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc); Frazer v. Schlegel, F.3d 1283, 1288 (Fed. Cir. 2007); and Centrak, Inc. v. Sonitor Tech., Inc., 915 F.3d 1360, 1369 (Fed. Cir. 2019).  The relevant P1 disclosure for CVC is that CRISPR is functional "when removed from its natural prokaryotic cellular milieu, which is highly relevant here because it establishes CVC's possession of the necessary and sufficient components for a functional CRISPR-Cas9 DNA-cleavage complex regardless of its environment" (emphasis in brief).

The argument is illustrated by Figures from the P1 application:

And explicit disclosure compared with the elements of the interference Count:

The brief then sets forth specific disclosure related to the elements of the Count (also provided in Appendix 3 entitled "Exemplary Evidence of Constructive Reduction to Practice of Count 1 in the P1 '068 Application"), and CVC further asserts that "[t]he inventors fully grasped the broad utility of such a method as aptly illustrated by the many types of 'target cells of interest' suitable for the methods described in P1, including a variety of eukaryotic cells (elements [1]-[2]) such as a fish, human, and fruit fly cell," noting that "[t]hese features are not merely recited in P1, but diagrammed, discussed, and specifically exemplified showing the inventors' possession" based on express disclosure cited with particularity in the brief (including specifically the prophetic use of CRISPR in fish cells).  CVC presents explicit argument relating to what the skilled worker would understand CVC possessed and would be able to accomplish without undue experimentation with regard to the CRTP requirement for being accorded benefit.  Finally, in this regard, the brief asserts that post-filing evidence (much of it by third parties) further supports a conclusion of constructive reduction to practice in the P1 disclosure:

Within a year of CVC publishing that Cas9 and a [single guide RNA] such as chimera A (or a double-molecule RNA) formed a functional DNA-cleavage complex (Ex. 3202), other researchers used materially the same components and methods disclosed in P1 to practice the fish cell embodiment—objectively confirming that P1 enables making and using the fish cell of E1.  While the studies described below published after P1's May 25, 2012 filing date, post-priority date evidence "may show, for example, that practicing the invention did not require undue experimentation," citing Amgen, Inc. v. Sanofi, 872 F.3d 1367, 1379 (Fed. Cir. 2017); In re Wands, 858 F.2d 731, 739 (Fed. Cir. 1988); In re Hogan, 559 F.2d 595, 605 (Fed. Cir. 1977).

CVC supports its allegations of what the skilled person would understand from the disclosure in the P1 specification by declaration testimony an expert, Dr. Peterson (who eventually will be subject to cross-examination by the Broad in this interference).  Specifically, Dr. Peterson attests extensively to the applicability of CRISPR as set forth in P1 to use in human cells, which CVC asserts is also shown by third-party success in applying CRISPR to human cells, and fruit fly cells.  Thus, CVC asserts "[i]n sum, the great weight of evidence compels a finding that P1 describes and enables each of the fish (E1), human (E2), and fruit fly (E3) cell methods, any one of which, on its own provides a CRTP of Count 1."

The brief then turns on the distinction between what was required for the Broad to prevail (as it did) in the earlier interference and in this one:

Broad's previously asserted arguments wrongly impose a reasonable expectation of success standard (obviousness) on §112, first paragraph, which contains no such standard.  Obviousness "turns on . . . whether the claimed invention would have been obvious in view of the prior art."  Allergan, Inc. v. Sandoz, Inc., 796 F.3d 1293, 1310 (Fed. Cir. 2015) (emphasis in original).  "In contrast, the enablement inquiry turns on whether the skilled artisan, after reading the specification, would be able to make and use the claimed invention without undue experimentation."  Id. (emphasis in original).  Similarly, "[t]he standard for satisfying the written description requirement is whether the disclosure 'allow(s) one skilled in the art to visualize or recognize the identity of the subject matter purportedly described.'"  Alcon, 745 F.3d at 1190 (emphasis added; citation omitted); see also, Ariad, 598 F.3d at 1351.  Any argument to the contrary erroneously conflates obviousness with written description and enablement.

Finally, the brief argues in the alternative that the other applications CVC asserts for priority contain the P1 disclosure relied upon for priority in this brief, and thus for the same reasons (set forth in brief for each reference) CVC is entitled to priority to these applications, based on the "continuous chain" of priority in these CVC applications.

Happy Thanksgiving from Patent Docs

The authors and contributors of Patent Docs wish their readers and families a Happy Thanksgiving.  Publication of Patent Docs will resume on November 30th.

The authors and contributors of Patent Docs wish their readers and families a Happy Thanksgiving.  Publication of Patent Docs will resume on November 30th.

The authors and contributors of Patent Docs wish their readers and families a Happy Thanksgiving.  Publication of Patent Docs will resume on November 30th.

CRISPR Motions Day at the PTAB: Broad Files Its Substantive Motion No. 2

By Kevin E. Noonan --

October 14th was a busy day at the Patent Trial and Appeal Board (PTAB) for the current interference over CRISPR technology (No. 106,115).  The Junior Party (the University of California, Berkeley; the University of Vienna; and Emmanuelle Charpentier; collectively, "CVC") filed its Substantive Motion No. 1 for priority benefit to its application No. 61/652,086, and its Opposition to the Senior Party's (the Broad Institute, Harvard University and MIT) Substantive Motion No. 1.  The Broad for its part filed three additional substantive motions (Contingent Motion No. 2 to substitute the count; No. 3 to designate claims as not corresponding to the count; and No. 4, for priority benefit to the Broad's application No. 61/736,528).  This post will discuss The Broad's Substantive Motion No. 2; future posts will review the remaining Broad motions and CVC's Substantive Motion No. 1.

This motion seeks to substitute the Count; Count 1 of the interference as declared is:

An engineered, programmable, non-naturally occurring Type II CRISPR-Cas system comprising a Cas9 protein and at least one guide RNA that targets and hybridizes to a target sequence of a DNA molecule in a eukaryotic cell, wherein the DNA molecule encodes and the eukaryotic cell expresses at least one gene product and the Cas9 protein cleaves the DNA molecules, whereby expression of the at least one gene product is altered; and, wherein the Cas9 protein and the guide RNA do not naturally occur together, wherein the guide RNAs comprise a guide sequence fused to a tracr sequence.

or

A eukaryotic cell comprising a target DNA molecule and an engineered and/or non-naturally occurring Type II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-— CRISPR associated (Cas) (CRISPR-Cas) system comprising
    a) a Cas9 protein, or a nucleic acid comprising a nucleotide sequence encoding said Cas9 protein; and
    b) a single molecule DNA-targeting RNA, or a nucleic acid comprising a nucleotide sequence encoding said single molecule DNA-targeting RNA; wherein the single molecule DNA-targeting RNA comprises:
        i) a targeter-RNA that is capable of hybridizing with a target sequence in the target DNA molecule, and
        ii) an activator-RNA that is capable of hybridizing with the targeter-RNA to form a double-stranded RNA duplex of a protein- binding segment,
    wherein the activator-RNA and the targeter-RNA are covalently linked to one another with intervening nucleotides; and
    wherein the single molecule DNA-targeting RNA is capable of forming a complex with the Cas9 protein, thereby targeting the Cas9 protein to the target DNA molecule, whereby said system is capable of cleaving or editing the target DNA molecule or modulating transcription of at least one gene encoded by the target DNA molecule.

The Broad's proposed Count 2 is:

A method, in a eukaryotic cell, of cleaving or editing a target DNA molecule or modulating transcription of at least one gene encoded by the target DNA molecule, the method comprising:
    contacting, in a eukaryotic cell, a target DNA molecule having a target sequence with an engineered and/or non-naturally-occurring Type II Clustered Regularly lnterspaced Short Palindromic Repeats (CRISPR)-CRISPR associated Cas) (CRISPR-Cas) system comprising:
        a) a Cas9 protein, and
        b) RNA comprising
            i) a targeter-RNA that is capable of hybridizing with the target sequence of the DNA molecule or a first RNA comprising (A) a first sequence capable of hybridizing with the target sequence of the DNA molecule and (B) a second sequence; and
            ii) an activator-RNA that is capable of hybridizing to the targeter-RNA to form an RNA duplex in the eukaryotic cell or a second RNA comprising a tracr sequence that is capable of hybridizing to the second sequence to form an RNA duplex in the eukaryotic cell,
    wherein, in the eukaryotic cell, the targeter-RNA or the first sequence directs the Cas9 protein to the target sequence and the DNA molecule is cleaved or edited or at least one product of the DNA molecule is altered.

The distinction the Broad makes is between embodiments of CRISPR methods that are limited to "single-molecule guide RNA" (aka "fused" or "covalently linked" species), versus embodiments that encompass single-molecule and "dual molecule" species (wherein the in the latter versions the "targeter-RNA" and "activator-RNA" as recited in the proposed Count are not covalently linked).  The Broad argues that this Count should be adopted by the Board because it "properly describes the full scope of the interfering subject matter between the parties because both parties have involved claims that are generic, non-limited RNA claims."  The brief also argues that proposed Count 2 "sets the correct scope of admissible proofs [i.e., their own] for the breakthrough invention described by the generic claims at issue in these proceedings—the successful adaption of CRISPR-Cas9 systems for use in eukaryotic environments," which The Broad contends current Court 1 (in either alternative) does not.

The brief also requests that the Broad be accorded benefit to its provisional application U.S. Serial No. 61/736,527, and that CVC not be accorded benefit to any of its earlier applications (which just maintains the status quo requiring CVC to move to be accorded benefit), because CVC's applications-in-interference were not accorded benefit when this interference was declared.

The Broad's argument in support of its motion is that Count 1 is too narrow for encompassing just a subset of the parties' involved claims.  In particular, the brief asserts that most of the Broad's involved clams encompass "non-limited" RNA systems and methods.  Similarly, the brief argues that CVC itself has many claims directed to non-limited RNA systems and methods and has entire applications that do not recite claims to non-limited RNA systems and methods.  The Broad asserts that Count 1 does not permit the Broad to rely on its earliest and best proofs of invention, which the brief states is "plainly unfair."  This unfairness would preclude the Broad from establishing what the brief terms "the fundamental breakthrough - the invention of use of CRISPR in eukaryotic cells" (emphasis in brief).  Failing to substitute the Count would instead improperly focus the priority question on who invented the single molecule modification.  Colorfully, the brief declares that "[a]llowing the interference to proceed with Count 1 would permit the (single molecule RNA) tail to wag the (breakthrough use of CRISPR in eukaryotic cells) dog."

The claims include such generic species that encompass both single-molecule and dual molecule embodiments, according to the brief, but the breakthrough invention was adapting CRISPR-Cas9 to be used in eukaryotic cells, an argument the Broad has used consistently here and in the earlier '048 interference to distinguish its claims from CVC's.  The brief notes that the first disclosure of this use was in a scientific journal article by some of the Broad's named inventors that "has become by far the most frequently cited CRISPR publication" as evidence of the groundbreaking nature of the invention.  Also cited (as a reminder to the Board of its earlier decision, the basis thereof and the Federal Circuit's affirmance of it) is the Board's earlier decision that there was no reasonable expectation of adapting CRISPR for use in eukaryotic cells as further evidence of the breakthrough nature of (as asserted herein) the Broad's invention.

It is then the Broad's turn to allege that its opponent is attempting to avoid this interference, "on fair terms," the question of which party invented use CRISPR in eukaryotic cells.  The Broad sets out its allegations against CVC, first for "tr[ying] to engineer" the '48 interference on "environment-free" proofs, and now for "trying to engineer a single-molecule RNA eukaryotic CRISPR interference" that would prevent the Broad from relying on its best (i.e., early dual molecule RNA) proofs.  Whereas, according to the Broad, CVC is attempting to rely on reduction to practice of single-molecule RNA systems that "occur[ed] over a year after Broad's alleged earliest reductions to practice" (emphasis in brief).  The consequence of using Count 1 would raise "'the anomalous possibility' that CVC could win priority as to the full scope of the commonly claimed invention (and Broad could lose all of its designated claims, including non-limited RNA claims) merely by CVC proving priority based on a later reduction to practice on a limited count, even though Broad made the broad invention of the designated claims first."

Further, echoing arguments made in its Substantive Motion No. 1, using such an "artificially narrow count" would permit CVC to avoid the estoppel effects of the decision in the '048 interference, according to the Broad.  The brief cites a CVC press release touting the risk this interference provokes that "jeopardizes all of the Broad's CRISPR patents as (somehow) being evidence that CVC is unfairly trying to obtain an undeserved windfall in its interference strategy (ignoring the fact that it was the PTO that declared the interference and determined the Count).

The Broad then provides the Board with, in the alternative, either proceeding with this interference under Count 1 but finding that non-limited RNA claims do not correspond to the Count, or proceeding with a two Count interference, with one Count directed to using CRISPR in eukaryotic cells and the other directed to single-molecule RNA species.

The brief then sets forth the differences between non-limited and single-molecule RNA versions of CRISPR, and its history of the development of its eukaryotic cell embodiments of CRISPR technology, making distinction between single-molecule RNA and dual molecule RNA embodiments, and liberally illustrating the brief with diagrams from its own NIH grant applications and scientific references.  The brief then synopsizes the decision in the earlier '048 interference based on there being no reasonable expectation of success in achieving eukaryotic cell applications of CRISPR based on earlier applications of CRISPR in prokaryotic cells.  This was followed by the Broad's description of the CVC's further prosecution of the applications in this interference.

Section V of the brief adopts the format of motions in interference practice of setting forth the basis for the PTAB to grant the motion.  For motions such as this one, the standard is that the current Count does not encompass the full scope of the interfering subject matter and excludes the Broad's best proofs.  See, Grose v. Plank, 15 U.S.P.Q.2d 1338, *4-6 (B.P.A.I. 1990); Kondo v. Martel, 220 U.S.P.Q. 49, *2-3 (B.P.A.I. 1983); Nelson v. Drabek, 212 U.S.P.Q. 98 *2-3 (Comm'r 1979).  The interfering subject matter, according to the Broad, is claims to non-limited RNA (i.e., single molecule and double molecule species of RNA) for use in eukaryotic cells; the grounds for this allegation is that each party has involved claims to this subject matter.  The crux of this argument (echoed throughout) is that "the Count should be set to resolve the parties' dispute as to who made the breakthrough necessary to make CRISPR Cas9 systems and methods work in a eukaryotic environment first, not just which party first disclosed 'fused' or 'covalently-linked' guide RNA," citing In re Van Geuns, 988 F.2d 1181, 1184 (Fed. Cir. 1993).  Doing otherwise (i.e., maintaining Count 1) would result (according to the Broad) in the Board awarding priority "not to the party that invented [use of CRISPR in eukaryotic cells] first, but rather to whomever can show they made the single molecule modification to that invention first."

The Broad contends that Count 1 puts all their claims at risk (a complaint contrary to arguments that the Board should settle the interference (in their favor) once an for all.  And the brief reiterates the allegation that this is fundamentally unfair because CVC made a "its deliberate decision to not include eukaryotic CRISPR claims in the 048 Interference, in which Broad could have used proofs commensurate in scope with the scope of its claims."

Next the Broad sets forth its arguments why the PTAB should grant the motion and substitute this Count 2.  First, according to the brief, Count 2 is consistent with the scope of the parties' claims and properly describe the scope of the interfering subject matter.  Because the Broad has proofs relating to using dual molecule RNA in CRISPR prior to CVC's claims-in-interference, and limiting their proofs to single molecule embodiments (which cannot antedate CVC's claims in interference) would limit the extent to which the Broad could counter CVC's priority proofs.  And as they have argued elsewhere, CVC's own public statements are used to imply that Berkeley and its colleagues are pursuing the broader scope because it puts essentially all the Broad's patents at risk (ignoring for the purpose of its argument that CVC did not provoke this interference or suggestion this Count No. 1, both of which are sua sponte creatures of the PTAB itself).

With regard to its "best proofs" argument, the Broad cites caselaw (Univ. of S. California v. DePuy Spine, Inc., 473 F. App'x 893, 23 895 (Fed. Cir. 2012)) the Board's regulations (37 C.F.R. § 41.121, § 41.201, and § 41.208(a)(2)); and the MPEP (MPEP § 2304.02(b)) in support of its position.  The brief supplements these citations with what CVC is "likely" to argue, i.e., "that Broad is barred from relying on some of its best proofs supporting priority as to its non-limited claims, which are the vast majority of its involved claims."  Those "best proofs" are duel-molecule guide RNA embodiments used in eukaryotic cells that the Broad contends are entitled to a filing date in 2012 earlier than any possible CVC priority date, based inter alia on affidavit testimony submitted with its brief in addition to declarations and laboratory evidence submitted during ex parte prosecution.  And of course the Broad reminds the Board that the consequence could be awarding priority to a later inventor, contrary to the purpose of interferences.

In the alternative, the Broad argues that should the PTAB determine that the estoppel the Broad argued in Substantive Morton No. 1 does not apply, and that the interference will proceed under Count 1, the PTAB should designate the Broad's claims directed to dual-molecule RNA embodiments as not corresponding to Count 1, or sua sponte declare a two Count interference.

The brief next turns to the benefit of priority to which they are entitled under Count 2, specifically the Zhang B1 reference and any intervening patents or applications claiming priority to USSN 61/736,527 (Zhang B1), illustrated by this diagram and supported by evidence set forth in Appendix 3:

The brief then sets forth, in detail, element-by-element, support in Zhang B1 for the recited elements of the Count.  Also recited is the asserted basis for priority in each of the related, later-filed applications set forth in the diagram, as well as the '945, '965, '445, '356, '814, '839, '616 and '713 Patents and '551 application, thus reaffirming that these patents-in-interference were entitled to the priority claim.

In contrast, the Broad argues that CVC is not entitled to any priority, based in part because there was no benefit of priority was accorded by the Board when this interference was declared.

Section V.F. then argues that Count No. 2 recites subject matter that is patentable over the prior art, when considered in light of the Broad being entitled to the December 12, 2012 filing date of the Zhang B1 reference, first by analogy to the subject matter of the Count in the '048 Interference (and, extensively, the PTAB's decision in that interference and the Federal Circuit' affirmance thereof) and also because the Broad's claims corresponding to Count No. 2 had been allowed over the prior art of record.

Finally, the Broad's brief argues which of its claims correspond to Count No. 2:

USP 8,697,359 – Claims 1-20 (all); USP 8,771,945 – Claims 1-29 (all); USP 8,795,965 – Claims 1-30 (all); USP 8,889,356 – Claims 1-30 (all); USP 8,906,616 – Claims 1-30 (all); USP 8,945,839 – Claims 1-28 (all); USP 8,993,233 – Claims 1-6 and 8-43; USP 8,999,641 – Claims 1-28 (all); USP 9,840,713 – Claims 1-41 (all); and UPS 14/704,551 – Claims 2, 4-8, and 12-18

And which do not (and arguments in support of its designations).  The brief also sets out which of CVC's claims so correspond (all of them).

Berkeley Files Opposition to Broad's Substantive Motion No. 1 in Interference

By Kevin E. Noonan --

On October 18th, Junior Party (the University of California, Berkeley; the University of Vienna; and Emmanuelle Charpentier (collectively, "CVC") filed its authorized opposition to Substantive Motion No. 1 from Senior Party the Broad Institute (and its partners as Senior Party, Harvard University and MIT), which asked for judgment in Interference No. 106,115 on the basis that CVC was estopped by prior judgment of no interference in fact in Interference No. 106,048 between these parties.

To recap, the Broad's motion asserted these arguments in favor of judgment:

CVC is estopped from getting a "second bite at the apple" in this interference by the provisions of 37 C.F.R. § 41.127(a)(1) and MPEP § 2308.03(b) (interference estoppel) because:

-     this interference is directed to the same subject matter as the previous '048 patent (using the inclusion of the same Broad patents in this interference and the correspondence between the count in the '048 interference and claim 1 in involve U.S. Patent No. 8,697,359 in support)

-     CVC is estopped from pursuing this interference on the grounds of judgment estoppel regarding issues that were raised or could have been raised in the earlier interference:

Judgment. (a) Effect within Office—(1) Estoppel.  A judgment disposes of all issues that were, or by motion could have properly been, raised and decided.  A losing party who could have properly moved for relief on an issue, but did not so move, may not take action in the Office after the judgment that is inconsistent with that party's failure to move, except that a losing party shall not be estopped with respect to any contested subject matter for which that party was awarded a favorable judgment [emphasis added].

The Broad argued that CVC had the opportunity in the '048 interference to file a responsive motion to the Broad's motion of no interference-in-fact to add claims directed to eukaryotic applications of CRISPR technology but did not.  The Broad argues that this was a strategic decision by CVC to have only its "environment-free" claims in the interference.  Furthermore, the Broad contends that it was intentional, citing to CVC's colloquy before the Board when the parties discussed which motion the Board would authorize, where CVC expressly "reserved" the ability to file such responsive motions.

The Broad's motion also asserts that the Board should not permit CVC to maintain the "cloud of uncertainty" regarding its patents, in its public statements and by pursuing "serial" interferences against the same Broad patents.

As is required under the procedural rules in interferences, CVC's opposition addresses each of these contentions in turn, including any disagreement over the facts the Broad put forward in support.  Thus, CVC's first asserted opposition argument was that "judgment estoppel" (quotation marks in opposition brief) does not exist in any form that would prelude this interference.  CVC's counter to the Broad's argument focuses on the existence vel non of a "losing" party in cases where no interference-in-fact are found.  The brief characterizes as false the assumption that the subject matter of this interference is the same as the subject matter of the '048 interference.  In the prior interference, it is undisputed that the Broad's claims were limited to practicing CRISPR in eukaryotic cells while CVC's claims-in-interference had no such restriction.  That restriction (embodied in the Count) was imposed by the Board when the '048 interference was declared (and the Board never ruled on CVC's motion to change the count to remove this restriction.  The scope of that earlier interference is different from this one, which is frankly directed towards using CRISPR solely in the eukaryotic background.  According to CVC, this is the first time the priority question on practicing CRISPR solely in the eukaryotic cell context has been before the Board, and thus there should be no estoppel.

With regard to the Broad's arguments related to Rule 127, CVC contends that the Broad has misconstrued the meaning of the first sentence of the Rule.  There is no per se "failure to move" requirement devoid of the need for a losing party in the prior interference (which does not exist in this case).  The brief takes the opportunity to assert its priority argument in this section, arguing that CVC was "the first party to file a patent application identifying the necessary and sufficient components of a CRISPR-Cas system that cleaves or edits DNA," starting with its May 25, 2012 filing date, importantly encompassing its use without regard to cellular milieu.

The brief further addresses the assertions made that CVC was executing a "tactical decision" to "wage [a] serial interference campaign."  On the contrary, CVC argues that it had suggested a count in the '048 interference that was cellular milieu-free, and it was the Board that restricted the count to use in eukaryotic cells.  Nor, CVC contends, can its efforts to obtain patents on systems and uses of CRISPR in eukaryotic cells as "a mere attack" on the Broad's claims.  CVC is jut doing what it was always intending to do, obtain broad and specific claim coverage for uses of CRISPR broadly.  CVC also reminds the Board that, unlike in the '048 interference in this interference the Board declared it sua sponte (further blunting any allegations of manipulation or scheming, according to CVC).  Having found interfering subject matter CVC argues that the Board ha a responsibility to declare an interference to resolve the priority issue under 35 U.S.C. §§ 102(g) and 135.  CVC further argues that it is the Broad that has sought to avoid Board determination of the priority question, and points to its alleged motivation to do so:  "[the] Broad was actually the fourth entity to file a patent application directed to CRISPR in eukaryotes" (citing facts CVC filed in support of tis opposition).  The brief also makes sub silentio an argument regarding the Broad's (perfectly proper) prosecution strategy that accelerated examination of its CRISPR patents, and by "changing its applications' designation from post-AIA to pre-AIA during prosecution so that it could swear behind CVC's earlier-filed application."  And CVC turns the Broad's victory in the earlier '048 interference against it, characterizing the Broad's successful pursuit of a finding of no interference-in-fact as another way to avoid final Board determination of the priority question (and similarly turns the Broad's allegations that CVC had a responsibility to move that the Board include claims to eukaryotic cell embodiments of CRISPR against the Broad, by alleging that it was the Broad that "could and should have moved to add a eukaryotic claim to CVC's involved application" as the proper alternative to seeking a finding of no interference-in-fact).  Reminding the Board of the purported advantages of its alleged strategy, the brief states that:

Broad has enjoyed the benefits of its issued patents for five-and-a- half years but must now finally face the unresolved question of priority of invention for CRISPR in eukaryotes; no principles of collateral estoppel or res judicata prohibit the PTAB from resolving the issue now via this interference.  Broad and the public have long been on notice that this issue remained unresolved as between Broad and CVC.  The present interference, mandated by §§ 102(g) and 135, presents the proper vehicle for finally resolving priority of invention.

CVC's brief also addresses the estoppel issue, stating that interpreting estoppel as the Broad seeks in its motion would "invite the Office to commit legal error by exceeding its authority."  Interference estoppel comes in two flavors, according to the brief:  those set forth expressly in the enabling statute and those arising from common law.  The latter are impliedly present in the statute because "Congress may be presumed, when enacting a statute granting to an agency adjudicatory authority, to mandate adherence to the doctrine of collateral estoppel," citing Duvall v. Atty. Gen., 436 F.3d 382, 387 (3d Cir. 2006).  Here, the statute does not affirmatively set forth an estoppel and thus, according to CVC, any estoppel (including the "judicial estoppel" that is the basis for the Broad's prayer for relief in its motion, must arise from these common law principles.  In addition, CVC argues that once Congress gives an agency authority to act, it "cannot promulgate or apply procedural rules in a manner that unilaterally contracts its jurisdiction to make it more narrow than what Congress has provided," citing Union Pac. R. Co. v. Bhd. 13 of Locomotive Engineers & Trainmen, 130 S. Ct. 584, 590 (2009).  These arguments are relevant to CVC brief in two ways:  first, the PTAB is not capable of promulgating rules on estoppel that go beyond the common law (absent express statutory authority absent here).  Nor can the PTAB fail to satisfy its statutory mandate (here) to make priority determinations when priority of invention is in conflict.

With regard to the proper scope of estoppel, CVC argues that the Broad's interpretation of Rule 127 is contrary to these common law estoppel principles.  CVC's first argument in support of its opposition in this regard is that this interference does not involve the same subject matter as the prior, '048 interference (making arguments substantially as set forth above on this point).  While it is true that the Broad's claims in the earlier interference were limited to eukaryotic cell applications of CRISPR, CVC's were not, and thus this interference considering eukaryotic cell claims of both parties defines different subject matter.  CVC's claims limited to eukaryotic cells in this interference are (and must be) patentably distinct from its claims in the '048 interference, because after all that distinction was the basis for the Broad having the PTAB (and the Federal Circuit) decide there was no interference-in-fact in the '048 interference:

The PTAB is now poised to answer who was first to invent CRISPR in eukaryotes.  That question was not (and could not have been) litigated or decided in the previous interference given the no interference-in-fact determination.  No principle of collateral estoppel or res judicata prevents deciding an issue that was not previously litigated,

according to CVC’s brief, citing B&B Hardware, Inc. v. Hargis Indus., Inc., 135 S. Ct. 1293, 1303 (2015); Biogen MA, Inc. v. Japanese Found. for Cancer Research, 785 F.3d 648, 658 (Fed. Cir. 2015); Purdue Pharma L.P., et al. v. Iancu, 2019 U.S. App. LEXIS 11205 (Fed. Cir. 2019); and Cromwell v. County of Sac, 94 U.S. 351, 353 (1877).

The brief makes a distinction between termination of an interference because no interference-in-fact is found (which, according to CVC, is a dismissal for lack of jurisdiction), which is not the same as a judgment and "does not preclude a second action based on the same cause of action that includes claims that overcome the initial defect of jurisdiction," citing, inter alia, Hughes v. U.S., 71 U.S. 232, 237 (1866).  The proper analogy for a finding of no interference-in-fact is dismissal of a district court action for failure to state a claim, where res judicata arises only where the defect in the pleadings has not been cured.

CVC further faults the Broad's estoppel argument by noting that according to its terms Rule 127 raises an estoppel in the context of provoking an interference, whereas the '115 interference was declared sua sponte by the Board (exactly the type of procedural argument that frequently resonates with the Board; see "Sigma-Aldrich Tried Again").  Similarly, CVC's brief distinguishes MPEP 2308.03(b) from MPEP 2308.03(c) on the basis that the former rule of practice bars "any further interference between the same 2 parties for claims to the same invention as the count of the interference, [and] not any subsequent interference that presents a new question not previously litigated" (emphasis in brief).  (And even if the PTAB disagrees with how CVC has parsed the MPEP, the brief asserts that "[t]o the extent that MPEP 2308.03(b) is construed to bar the present interference, the MPEP is contrary to the law and therefore invalid.")  Finally, on these matters CVC disagrees that the scope of the count of the '048 interference has any weight or relevance, because if there was no interference-in-fact in the '048 interference there was no count that properly defined interfering subject matter.

CVC's brief then turns to the Broad's argument that CVC was under an obligation to move to include claims in the '048 interference directed to eukaryotic embodiments of CRISPR and that failing to do so raises an estoppel.  Here CVC again raises objection to the Broad's interpretation of Rule 127, asserting (again) that the Rule requires there to be a losing party for estoppel to arise and a finding of no interference-in-fact does not produce a losing party.  (The brief cites voluminous authority regarding the proper relationship between clauses or provisions of rules or statutes and their interpretation in support of this argument.)  The brief notes (at least in part in contrast) that the Broad cited no authority for its (mis)interpretation of the Rule, and that its citation of commentary on the rulemaking that resulted in the provisions of the MPEP cited in the Broad's brief either does not support the Broad's interpretation of the Rule nor is the Board bound by them.  CVC's conclusion is that:

[N]either Rule 127's text nor the rule-making comments state or imply that, following a judgment of no interference-in-fact, a non-losing party "who could have properly moved for relief on an issue, but did not so move, may not take action in the Office after the judgment that is inconsistent with the party's failure to move."  37 C.F.R. § 41.127(a)(1).  That kind of failure-to-move estoppel is expressly reserved for a losing party, and limited to issues for which the losing party was not awarded favorable judgment.  Id.  Applying estoppel any more broadly would impose an inequitable result on a party that had not lost the prior proceeding.

CVC further blunts (or attempts to do so) in this portion of the brief the Broad's allegations that CVC's actions or inaction in the prior '048 interference were somehow improper or merely strategic, calling these characterizations a "mischaracterize[ation of] the facts."  At least one set of these facts set forth in CVC's brief is that the Broad accuses CVC of not moving to include eukaryotic cell CRISPR claims in the '048 interference, when CVC had no such claims in condition for allowance (a requirement for the PTAB to make a priority determination) at that time.  CVC also cites a Board Order in the prior interference, which stated that "[u]nder the facts and circumstances of this interference, where [CVC] believes all of its current claims interfere with all of Broad's claims, there is no reason why [CVC] should need to add a new claim.  If [CVC]'s claims in other applications are ultimately found to be allowable, [CVC] may suggest additional interferences to the examiner" (emphasis in brief).  Clearly, the position argued by the Broad is contrary to the terms of the Board's prior Order (at least as CVC interprets it) and may provide a basis for the Board to disregard this portion of the Broad's argument at a minimum and perhaps deny Substantive Motion No. 1.

The final Sections of CVC's brief address the Broad's assertion of equitable estoppel (which, according to CVC, would result in the Board to "abrogate its statutory mandates to decide interferences under § 135 and to issue patents to all those entitled to them under § 102); certain "policy considerations" that support the PTAB deciding the priority question ("it would contradict the PTAB's legislative mandate if it were to refrain from deciding the outstanding priority of invention issue, particularly where Broad's patents are facially invalid in view of CVC's earlier filed patent applications disclosing CRISPR in eukaryotes"); and that the Board must resolve certain disputed factual issues before deciding to grant the Broad's Substantive Motion No. 1.

Final Section VI of the brief provides CVC with an outcome that could snatch (ultimate) victory from the jaws of a defeat should the Board grant the Broad's Substantive Motion No. 1.  Under those circumstances, CVC argues that the PTO has determined that CVC's claims are in condition for allowance but for the priority issues that have arisen under 35 U.S.C. §102(g).  Thus, should the Board grant the Broad's motion the impediments to patentability raised by the Examiner would be overcome (i.e., there would be no violation of § 102(g)) and accordingly the Office should issue CVC's patents in due course.  This would then give CVC the right to file an action in district court under § 291 to determine which of CVC and the Broad should properly have priority to the subject matter of eukaryotic cell embodiments of CRISPR.  While not exactly a poison pill, such an outcome would not necessarily be estopped, because there would be two parties having granted claims to eukaryotic embodiments of CRISPR, and the public interest at a minimum would favor final resolution of the priority question.  Of course the Broad recognized the possibility of this outcome and has asserted § 101 as a basis to preclude the Office from granting CVC's patents. While § 101 has been put to a great many uses during the past ten years, it clearly does not apply here (as CVC asserts), because "§ 101 simply bars issuing two patents to the same inventive entity; it says nothing about issuing a patent to a different inventive entity" (which is the provenance of § 102(g)).

The Broad's Reply brief is due March 20, 2020 unless the Board specifies an earlier date (which is likely).

Board Denies CVC Motion to Seal Priority Statement

By Kevin E. Noonan --

On September 11th, Junior Party (Regents of the University of California, University of Vienna, and Emmanuelle Charpentier, collectively "CVC") in Interference No. 106,115 with The Broad Institute et al. filed a motion to file its priority statement under seal.  Specifically, CVC's motion requested that it be permitted to have the PTAB seal the priority statement until 45 days after final judgment or indefinitely; CVC also asked for 45 days after judgment to move that the statement be expunged from the record.  (In the alternative, CVC requested that its statement remain sealed until a scheduling order issued by the Board for the priority phase of the interference, and that CVC be permitted to file a motion to expunge, e.g., if the count was changed).  Last week, the Patent Trial and Appeal Board (PTAB) denied this motion, in a Decision by Administrative Patent Judge Katz, joined by APJs Moore and Lane.

CVC's motion was based on their contention that their priority statement "will contain sensitive research and development information that would be otherwise kept confidential."  CVC asserted that there were "several third-party competitors [specifically, Sigma-Aldrich, ToolGen, and Vilnius University] in the field of CRISR-Cas9 gene editing technology and that it will be prejudiced in any potential interference with these parties if its confidential research and development information were to be made public."  These competitors, according to CVC, all have competing applications filed within 10 months of CVC's priority date, and have argued that their claims interfere with CVC's claims in this interference (see "Sigma-Aldrich Wants Its Piece of CRISPR Pie").

The Board opined that, in agreement with the Broad, CVC's arguments were "based on speculation," because as yet there have been no other interferences declared between CVC and any of these other parties.  Relying as it frequently does on the procedural aspects of the questions before it (see "Sigma-Aldrich Tries Again"), the Board asserts in support of this point that "no count has been used to describe interfering subject matter between any of CVC's applications or patents" and that "CVC presents no evidence that any of the claims it asserts might interfere with CVC's own claims have been determined to be allowable."  Under these circumstances, the Board was not persuaded to deviate from its policy that "[t]he record of a Board proceeding [be] available to the public unless a patent application not otherwise available to the public is involved," citing 37 C.F.R. § 41.6(b)(1).  In particular, the opinion reminds the parties that the Board "strive[s] towards making all filings in an interference public at least by the time we issue a final judgment," and that CVC has requested that its priority statement be held under seal until 45 days after final judgment (although the Board notes that CVC can file a renewed request once judgment has been entered).

The Board was persuaded by CVC's request to keep its priority statement under seal until the Board issued a schedule for the priority phase, stating that CVC had correctly noted that 37 C.F. R. § 41.120(a) permits the Board to keep priority statements confidential "for a limited time."  The Board remained unpersuaded by the Broad's arguments that it would be prejudiced, inter alia, because "Broad's potential licensees, commercial partners, and the public will not be able to evaluate for themselves CVC's claims to priority, and Broad's patents will continue to be subject to the uncertainty CVC has sought to create around them since suggesting the 048 interference four years ago."  The opinion states in support that the parties' priority evidence will not be "made in full" until priority motions are filed if there is a priority phase in this interference.  And the Board does not see prejudice to the Broad's ability to establish priority if CVC's priority statement is kept in confidence until the priority phase commences.

The opinion mandates that CVC file by November 7th a revised proposed protective order taking into account the Board's decision to keep CVC's priority statement under seal until commencement of the priority phase.

Patent Docs Celebrates 13 Years of Operation

Thirteen years ago today, we began publishing Patent Docs, a weblog that initially focused on recent developments in biotech and pharma patent law, and has since expanded to cover all things patent-related.  After thousands of posts and millions of words; after the claims-and-continuation rules debacle; the America Invents Act and all the bills that preceded it; the BPCIA from its enactment to recent interpretation by the courts; Bilski, Mayo, Myriad, Alice, Sequenom, and Athena; Ariad and KSR; Dudas, Rogan, Rea, Kappos, Lee, and Iancu, we have been blessed by our readers and patent law's seemingly inexhaustible number of interesting (and occasionally frustrating) things to write about.  We look forward to the future, and having you all with us.  Thanks for reading.

Phigenix, Inc. v. Genentech, Inc. (Fed. Cir. 2019)

By Donald Zuhn --

Earlier this month, in Phigenix, Inc. v. Genentech, Inc., the Federal Circuit affirmed a decision by the U.S. District Court for the Northern District of California striking the infringement opinion of Phigenix's expert and granting summary judgment of noninfringement based on a lack of evidence of both direct infringement and intent to induce infringement.  The District Court also denied summary judgment of invalidity of Phigenix's U.S. Patent No. 8,080,534.

The '534 patent, which is entitled "Targeting PAX2 for the Treatment of Breast Cancer," describes preventing or treating breast conditions (including breast cancer) by administering a composition that inhibits and/or enhances the expression of certain genes (PAX2 and DEFB1, respectively).  Claim 1 recites "[a] method for treating a breast condition" by administering a composition that inhibits PAX2 expression or activity, and/or expresses DEFB1.

Phigenix filed suit against Genentech for infringement of the '534 patent based on Genentech's product Kadcyla, alleging that Genentech induced infringement of the '534 patent by encouraging health care professionals to prescribe and administer Kadcyla to breast cancer patients who had previously received the chemotherapy drugs "trastuzumab and a taxane, separately or in combination."  After the District Court issued an order holding that the asserted claims of the '534 patent are not entitled to the priority date of a 2005 provisional application, Phigenix narrowed the relevant population to Kadcyla patients who were pretreated exclusively with trastuzumab and a taxane (i.e., trastuzumab, a taxane, and "and nothing else"), which Phigenix conceded comprise only about 4% of the total population of Kadcyla patients.  However, Phigenix did not move to amend its infringement contentions to reflect this narrower population (Genentech learned of Phigenix's narrowed population definition during its deposition of Phigenix's expert after the close of fact discovery and months after the District Court's order regarding priority to the 2005 provisional application).

Genentech responded to the narrowed patient population by moving to strike the infringement opinion of Phigenix's expert.  The District Court, agreeing with Genentech that Phigenix had failed to provide adequate notice of its narrowed infringement theory, struck Phigenix's expert infringement opinion and granted summary judgment of noninfringement based on the lack of direct infringement evidence.  The District Court also granted summary judgment of noninfringement based on a lack of evidence of specific intent to induce infringement under Phigenix's narrowed theory.  Phigenix appealed the District Court's decision to strike its expert's noninfringement opinion and grant of summary judgment of noninfringement.

In an opinion by Judge Stoll, joined by Judges Reyna and Bryson, the Federal Circuit determined that the District Court was within its discretion to exclude the infringement opinion of Phigenix's expert in response to Phigenix's failure to timely disclose its narrowed infringement theory.  The panel noted that Phigenix narrowed the relevant patient population from "Kadcyla patients who were pretreated with trastuzumab and a taxane" to "Kadcyla patients who were pretreated with trastuzumab and a taxane and nothing else," and did so not in response to new evidence or a claim construction.  More importantly, the opinion notes that "it is clear that Phigenix did not take any deliberate action to proactively put Genentech on notice that it had [narrowed the relevant patient population]."  The panel also noted that it agreed with the District Court "that such a dramatic narrowing at such a late stage in the litigation prejudiced Genentech because it 'markedly transformed the nature of the infringement theory, and consequently, impacted Genentech's ability to prepare a defense.'"

In affirming the District Court's decision to strike the noninfringement opinion of Phigenix's expert and grant of summary judgment of noninfringement, the Federal Circuit found unpersuasive Phigenix's arguments that the District Court had abused its discretion.  The panel first disagreed with Phigenix's argument that its revised infringement theory was not newly propounded because it fell wholly within the scope of its original infringement contentions.  The panel, however, agreed with the District Court "that the broader theory disclosed in Phigenix's infringement contentions is not sufficiently specific to disclose its narrowed theory."  The panel also disagreed with Phigenix that it had put Genentech on notice of its narrowed infringement theory during a challenge to the prior art status of a particular clinical trial.  The panel was also not persuaded by a number of district court decisions cited by Phigenix, which Phigenix argued allowed plaintiffs to narrow their infringement theories after propounding broader infringement contentions.  In response, the Court noted that "on the merits, these cases are readily distinguishable because the moving party in each demonstrated early notice, diligence, new evidence, and/or leave obtained from the district court—none of which apply here."  Finally, the Court disagreed with Phigenix's argument that the District Court's decision to strike the entirety of Phigenix's expert's opinion was "heavy-handed," that Genentech had not adequately explained how it was prejudiced by the revised infringement theory, that Genentech had failed to explain why a less severe sanction would not address the District Court's concerns, and that Genentech had not sought clarification of Phigenix's infringement contentions.  The Court countered that "Genentech adequately explained how it was prejudiced by Phigenix's untimely narrowing of its infringement theory."

Rejecting Phigenix's arguments that the District Court had abused its discretion in striking the noninfringement opinion of Phigenix's expert, and without its expert report, the panel determined that Phigenix's direct infringement case must fail, and therefore affirmed the District Court's grant of summary judgment of noninfringement.

Phigenix, Inc. v. Genentech, Inc. (Fed. Cir. 2019)
Nonprecedential disposition
Panel: Circuit Judges Reyna, Bryson, and Stoll
Opinion by Circuit Judge Stoll

CRISPR Interference Parties Propose Motions

By Kevin E. Noonan --

The parties (University of California/Berkeley, the University of Vienna, and Emmanuelle Charpentier, Junior Party, and The Broad Institute, Massachusetts Institute of Technology, and Harvard University, Senior Party) to the newly declared interference over patents for CRISPR technology (see "CRISPR Battle Joined Again"), yesterday submitted to the Patent Trial and Appeal Board their proposed motions for the initial phase of the interference.  As is typically the case in these submissions, each party filed motions to place them in the best procedural position for the main event in the interference, a determination of who deserved priority to CRISPR, specifically embodiments of the technology for use in eukaryotic cells.

As a reminder, an interference proceeds in two stages.  The first stage involves the parties presenting motions that can modify the count, have certain claims declared outside the scope of the count (or vice versa), seek to establish an earlier priority date, and ask for a finding that their opponents' claims are invalid under any of the provisions of the patent statute.  If these motions are not decided in a way that would disqualify one or both parties, then the interference will move to a second stage, where the Junior Party (Berkeley, unless it can establish an earlier priority filing date) will present its proofs of conception and reduction to practice and the Senior Party will be permitted to oppose.  The Senior Party is under no obligation to present proofs earlier than its earliest filing date unless the Junior Party evinces evidence of (at least) earlier conception.  In practice, the parties can both be expected to submit their priority evidence.

Berkeley's motions reflected their position before the U.S. Patent and Trademark Office during examination that they deserve priority to eukaryotic embodiments of CRISPR (despite the decisions to the contrary by the PTAB and the Federal Circuit).  Under the acronym "CVC" (for California, Vienna, and Charpentier, the three parties challenging the Broad's entitlement to eukaryotic CRISPR), Junior Party's Motion 1 is an "expedited" miscellaneous motion under 37 C.F.R. § 41.121(a)(3) for benefit of an earlier non-provisional application and for the Board to redeclare the interference with CVC as the Senior party.  The basis for this motion is that the specification of the applications-in-interference have an identical specification to CVC's USSN 13/842,859, filed 3/15/2013 (pre-AIA).  CVC asks the Board to take these actions sua sponte because identical specifications are entitled to priority under 35 U.S.C. § 120.  To aid the Board, CVC provides in an Appendix a diagram showing how its applications are related:

Interestingly, PTO documents show that the Examiner and interference specialists recommended giving CVC the priority benefit to the '859 application.

CVC's Motion 2 requests benefit of priority to earlier provisional and non-provisional applications, specifically:

[E]ach of CVC's involved applications 15/947,680; 15/981,807; 16/136,168; and 16/136,175 is a continuation of U.S. Patent Application No. 14/685,504 ("the '504 application"), filed on April 13, 2015.  Each of CVC's involved applications 15/947,700; 15/947,718; 15/981,808; 15/981,809; 16/136,159; and 16/136,165 is a continuation of U.S. Patent Application No. 15/138,604 ("the '604 application), filed on April 26, 2016, which in turn is a continuation of the '504 application.  The '504 application is a continuation of U.S. Patent Application No. 13/842,859 ("the '859 application"), filed on March 15, 2013, which claims priority benefit to each of the following provisional applications: U.S. Provisional Application No. 61/652,086, filed on May 25, 2012 ("the '086 provisional" or "Provisional 1"); U.S. Provisional Application No. 61/716,256, filed on October 19, 2012 ("the '256 provisional" or "Provisional 2"); U.S. Provisional Application No. 61/757,640, filed January 28, 2013 ("the '640 provisional" or "Provisional 3"); and U.S. Provisional Application No. 61/765,576 ("the '576 Provisional" or "Provisional 4"), filed on February 15, 2013.

In view of the extensive history of these filings, CVC asks the Board to increase the page limit for its brief.

Motion 3, under 37 C.F.R. § 41.121(a)(1), asks the Board to treat the Broad's claims under the changes in the law effected by the Leahy-Smith America Invents Act with regard to Section 102 and 103 of the Patent Act, and for judgment that these claims are unpatentable under 35 U.S.C. § 103 over U.S. Patent Application Publication No. 2016/0298138 to Sigma in view of extensive prior art (122 references) contained in another Appendix.  Ironically, this application is the basis for Sigma-Aldrich's "extraordinary" petition for the PTAB to redeclare the interference (see "Sigma-Aldrich Wants Its Piece of CRISPR Pie") to include this application.  The basis for Motion 3 is that the Sigma application was filed six days earlier than the earliest Broad priority application, and that due to irregularities in the Broad's filing, they cannot "swear behind" this reference.  Once again, CVC asks the Board to increase the page limits on this motion (in this case because there are 415 involved Broad claims at issue).  CVC also submits a contingent motion, Motion 4 for judgment of unpatentability if the Broad applications and patents are entitled to pre-AIA treatment, under 35 U.S.C. § 103 over US 2016/0298138 to Sigma in view of extensive prior art contained in the Appendix.

CVC's Motion 5, under 37 C.F.R. § 41.121(a)(1) asks for judgment of unpatentability under 35 U.S.C. § 102(f) or (if post-AIA) 35 U.S.C. § 115(a) for "failure to name all inventors of the alleged invention.  [According to its proposal] CVC will demonstrate that Broad deliberately misidentified the inventors on its involved patents and applications . . . ."  Proper inventorship is important in the interference, inter alia, because the Board needs to know whose testimony can corroborate and whose needs to be corroborated under interference practice, where the uncorroborated testimony of an inventor is given no weight; see, Kolcraft Enters. v. Graco Children's Prods., Nos. 2018-1259, 2018-1260, 2019 U.S. App. LEXIS 19751 (Fed. Cir. July 2, 2019).  The factual bases for this motion are differences between the named inventors in the patents- and applications-in-interference and the inventors named in a declaration by the Broad's patent attorney during a European opposition (EP 277146); it may be recalled that such irregularities involving a Rockefeller University inventor (Dr. Luciano Marraffini) not named in the EP application was the basis for that patent to be invalidated (see "The CRISPR Chronicles -- Broad Institute Wins One and Loses One").

CVC's most aggressive proposed motion is Motion 6 under 37 C.F.R. § 41.121(a)(1) for inequitable conduct.  According to CVC, "Broad made at least one affirmative material misstatement during prosecution of each of Broad's involved patents, applications, or parent applications to which they claim priority" -- specifically, in a declaration by named inventor Zhang regarding actual reduction to practice of CRISPR-Cas9 in eukaryotic cells prior to May 2012.  CVC asserts that these statements are untruthful because the CRISPR system did not comprise tracrRNA, which is necessary for CRISPR to be functional.  CVC attempts to avoid the fate of a similar motion from the first CRISPR interference (for which the Board denied permission) on grounds that it is undisputed that tracrRNA is necessary for CRISPR function, using disclosure from U.S. Provisional Patent Application No. 61/736,527 as well as in the Broad's involved patents and independent prior art.  CVC also asserts that Zhang's "conception" arose only after reading a Berkeley prior art disclosure.  The proposal for this motion extensively analyzes purported evidence for actual reduction to practice to show the Broad's asserted failure, alleging that the Broad "cherry-picked data" that "intentionally omitted the context that shows his claims of successful DNA cleavage to be false."  This motion applies to all the Broad's patents- and applications-in-interference because the alleged untruthful statements were submitted in all applications.

CVC also makes similar allegations for another declaration submitted by a different inventor, which they contend evinced "a larger pattern of deception."  These allegations are supported by an e-mail from a Zhang lab member and named inventor on the Broad's provisional application (albeit in a context where there seems to exist an ax to grind against Dr. Zhang):

The 15-page declaration of [Feng Zhang] and Le Cong's luciferase data is mis- and overstated to change the examiner's decision, which seems to be a joke. . . .

After seeing your in virto [sic, in vitro] paper, Feng Zhang and Le Cong quickly jumped to the project without letting me know.  My lab notebooks, emails and other files like dropbox or gel pictures recorded every step of the lab's failure process.  I am willing to give more details and records if you are interested or whoever is interested to clear the truth. . . .

We did not work it out before seeing your paper, it's really a pity.

CVC's final Motion 7 is a miscellaneous motion under 37 C.F.R. § 41.121(a)(3) to add CVC's U.S. Application Nos. 16/276,361; 16/276,365; 16/276,368; and 16/276,374 to the interference.  CVC also provides a pro forma motion for priority, to be decided during the priority phase of the interference if it is not resolved beforehand.

The Broad's motions are predicated on their contention that this interference is "barred by res judicata, collateral estoppel, and law of the case" over the earlier-concluded interference (No. 106,048).  The Broad notes that the difference between the Count of the '048 interference and the Count in this interference as declared is that the prior Count did not require specific (covalent) linkage or fusion between the guide and tracr sequences, whereas that linkage was the basis for allowability of CVC's applications in this interference.  Accordingly, the Broad asks the PTAB to limit claims in interference to those having this limitation.  The Broad's Motion 1 under 37 C.F.R. §§ 41.121(a)(1)(iii) and 41.208(a)(1) is for judgment based on interference estoppel, citing MPEP § 2308.03(b): "A judgment of no interference-in-fact bars any further interference between the same parties for claims to the same invention as the count of the interference."  The Broad asks that this motion be expedited.  Motion 2 under 37 C.F.R. §§ 41.121(a)(1)(iii) and 41.208(a)(1) is related, for judgment based on CVC's failure to add a claim in the '048 interference reciting the linkage limitation, citing Woods v. Tsuchiya, 745 F.2d 1571, 1582 (Fed. Cir. 10 1985), and Ex parte Aoki, No. 2012-010117, 2015 WL 3827164 (P.T.A.B. June 15, 2015), for support.  The Broad further requests the Board issue a Notice to Show Cause (sub silentio apparently characterized as "Motion 3") why this interference is not precluded by judgment in the earlier '048 interference, based on the "showing" that CVC cannot antedate actual reduction to practice of applying CRISPR to eukaryotic cells in view of evidence of record in the '048 interference (CVC "cannot win on the merits" according to this portion of the Broad's argument).

As a hedge against failing to prevail on these motions, Motion 4 (contingent) under 37 C.F.R. §§ 41.121(a)(1)(i) and 41.208(a)(2) asks the Board to substitute the count with an alternative count that would be "broad enough to cover Broad's best proofs," specifically:

Proposed Count 2

A method comprising:
introducing into, or expressing in, a eukaryotic cell having a DNA molecule,
(I) a Cas9 protein or a nucleotide sequence encoding the Cas9 protein, and 
(II) RNA or a nucleotide sequence encoding the RNA, the RNA comprising:
    (a) a targeter-RNA or a first RNA, the first RNA comprising a first ribonucleotide sequence and a second ribonucleotide sequence, and
    (b) an activator-RNA or a second RNA,
wherein (II) (a) and (II) (b) are fused to one another or are covalently linked to one another with intervening nucleotides; and
wherein, in the eukaryotic cell, the activator-RNA or the second RNA form an RNA duplex with the targeter-RNA or the second ribonucleotide sequence, and the targeter-RNA or the first ribonucleotide sequence directs the Cas9 protein to a target sequence of the DNA molecule, and the DNA molecule is cleaved or edited or at least one product of 20 the DNA molecule is altered.

Should the Board substitute the present Count for this one, the Broad argues that only "claims 4, 11, and 18 of U.S. Patent No. 8,697,359; claim 5 of U.S. Patent No. 8,771,945; claim 5 of U.S. Patent No. 8,906,616; and claim 8 of U.S. Patent No. 8 9,840,713" should remain in the interference. Similar Motion 5 (contingent) under 37 C.F.R. 1 §§ 41.121(a)(1)(i) and 41.208(a)(2) asks the Board to substitute or add Count 3 to the interference:

Proposed Count 3

A method, in a eukaryotic cell, of cleaving or editing a target DNA molecule, or altering expression of at least one product encoded by the target DNA molecule, the method comprising:
    contacting, in a eukaryotic cell, a target DNA molecule having a target sequence with an engineered and/or non-naturally-occurring Type II Clustered 8 Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated 9 (Cas) (CRISPR-Cas) system comprising:
a) a Cas9 protein,
and
b) RNA comprising
    i) a targeter-RNA that is capable of hybridizing with the target sequence of the DNA molecule or a first RNA comprising (A) a first sequence capable of hybridizing with the target sequence of the DNA molecule and (B) a second sequence; and
    ii) an activator-RNA that is capable of hybridizing to the targeter-RNA to form an RNA duplex in the eukaryotic cell or a second RNA comprising a tracr sequence that is capable of hybridizing to the second sequence to form an RNA duplex in the eukaryotic cell,
wherein, in the eukaryotic cell, the targeter-RNA or the first sequence directs the Cas9 protein to the target sequence and the DNA molecule is cleaved or edited or at least one product of the DNA molecule is altered.

This claim is ("essentially") identical to the Count of the '048 interference for which the Broad asserts another "best proofs" justification.  The Broad takes the position that CVC would be estopped from showing priority to claims corresponding to this count based on the outcome of the '048 interference.

Motion 6 through Motion 9, all under 37 C.F.R. §§ 41.121(a)(1)(iii) and 41.208(a)(2) ask the Board to designate most of the Broad's claims as not corresponding to any or various permutations of the counts, in an effort to limit the Broad's exposure to losing their claims.  Motion 10 under 37 C.F.R. §§ 41.121(a)(1)(ii) and 41.208(a)(3) requests priority benefit of the Broad's prior applications, having an earliest priority date of December 12, 2012; in view of the extensiveness of the list the Broad requests "at least" 35 pages for its motion and brief.  Motion 11 under 37 C.F.R. §§ 41.121(a)(1)(iii) and 41.208(a)(1) seeks judgment against Berkeley on the grounds that the CVC claims are unpatentable for failure to satisfy the written description and/or enablement requirements of 35 U.S.C. § 112(a) and under 35 U.S.C. § 102(a) and/or 35 U.S.C. § 102(e) and 35 U.S.C. § 103, based on "the PTAB's binding finding that a POSA in 2012 would require the results of successful eukaryotic experiments to have a reasonable expectation of success that CRISPR-Cas9 could be made to work in eukaryotic cells, and given that D1 and D2 indisputably fail to disclose any eukaryotic experiments," and citing numerous scientific references (including Broad references).  And Motion 12 under 37 C.F.R. §§ 41.121(a)(3) asks the Board to require CVC to keep the Broad and the Board apprised of any notice of allowance in any pending, related applications.  Finally, the Broad also submits a pro forma motion for priority.

The Board has set August 5th as the date for a teleconference with the parties jointly; shortly thereafter (typically less than a week) the Board will issue an Order notifying the parties as to which motions they are authorized to file and which have been deferred or denied.  During the call the parties are able to inform the Board more specifically of the bases for their motions, provide a proffer if the Board needs additional evidence or information, and provides opposing parties the opportunity to give the Board their views.  With the Order on which motions are permitted the Board will also set a briefing schedule; a sample schedule is as follows:

TIME PERIOD 1

File motions
File (but serve one business day later) priority statements

TIME PERIOD 2

File responsive motions to motions filed in TIME PERIOD 1

TIME PERIOD 3

File oppositions to all motions

TIME PERIOD 4

File all replies

TIME PERIOD 5

File request for oral argument
File motions to exclude evidence
File observations

TIME PERIOD 6

File oppositions to motions to exclude
File response to observations

TIME PERIOD 7

File replies to oppositions to motions to exclude

DEFAULT ORAL ARGUMENT DATE

The Board permits the parties to stipulate to extensions and revisions to the schedule except for the last three dates; the oral argument date is (relatively) inviolate (unless the Board needs to reschedule) and occurs about seven months after the end of Time Period 1.

Patent Docs will provide the details of the Board's decisions on which motions it will permit the parties to file when they become available.

Sigma-Aldrich Wants Its Piece of CRISPR Pie

By Kevin E. Noonan --

On Friday, Sigma-Aldrich filed a self-described "extraordinary" petition to the Director of the U.S. Patent and Trademark Office (under 37 C.F.R. §§ 1.181-1.183) and the Chief Judge of the PTAB (under 37 C.F.R. § 41.3 and § 41.103), asking that the USPTO declare an interference between itself and the University of California, Berkeley "parallel" to the one recently declared between Berkeley and the Broad Institute and its companion institutions (see "CRISPR Battle Joined Again").

The petition is extraordinary because Sigma's claims are not in condition for allowance, which is a prerequisite for the Office declaring an interference.  The basis for Sigma's prayer for extraordinary relief is that the Examiner reviewing its pending applications, U.S. Application Nos. 15/188,911, 15/188,924, and 15/456,204, has refused to find that two Berkeley provisional applications (U.S. Application Nos. 61/652,086 and 61/716,256) do not anticipate nor render obvious its claims to applications of CRISPR in eukaryotic cells, despite determinations to the contrary with regard to Broad et al. patents having later priority dates by the Patent Trial and Appeal Board (see "PTAB Decides CRISPR Interference -- No interference-in-fact" and "PTAB Decides CRISPR Interference in Favor of Broad Institute -- Their Reasoning") and Federal Circuit (see "Regents of the University of California v. Broad Institute, Inc. (Fed. Cir. 2018)").  The very similar claims in Sigma's three pending applications read as follows:

U.S. Application No. 15/188,911:

1.  A method for integrating an exogenous sequence into a chromosomal sequence of a eukaryotic cell, the method comprising:
    a) introducing into the eukaryotic cell (i) at least one RNA-guided endonuclease comprising at least one nuclear localization signal or codon-optimized nucleic acid encoding at least one RNA-guided endonuclease comprising at least one nuclear localization signal, wherein the at least one RNA-guided endonuclease is a clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR associated (Cas) (CRISPR-Cas) type II system protein and the CRISPR-Cas type II system protein is a Cas9 protein, (ii) at least one guide RNA or DNA encoding at least one guide RNA, and (iii) at least one donor polynucleotide comprising the exogenous sequence; and
    b) culturing the eukaryotic cell such that the at least one guide RNA guides the at least one RNA-guided endonuclease to a target site in the chromosomal sequence where the RNA-guided endonuclease introduces a double-stranded break, the target site in the chromosomal sequence is immediately followed by a protospacer adjacent motif (PAM), and repair of the double-stranded break by a DNA repair process leads to integration of the exogenous sequence into the chromosomal sequence.

U.S. Application No. 15/188,924:

1.  A method for modifying a chromosomal sequence in a eukaryotic cell, the method comprising:
    a) introducing into the eukaryotic cell (i) at least one RNA-guided endonuclease comprising at least one nuclear localization signal or codon-optimized nucleic acid encoding at least one RNA-guided endonuclease comprising at least one nuclear localization signal, wherein the at least one RNA-guided endonuclease is a clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR associated (Cas) (CRISPR-Cas) type II system protein and the CRISPR-Cas type II system protein is a Cas9 protein, (ii) at least one guide RNA or DNA encoding at least one guide RNA, and, optionally, (iii) at least one donor polynucleotide; and
    b) culturing the eukaryotic cell such that the at least one guide RNA guides the at least one RNA-guided endonuclease to a target site in the chromosomal sequence where the RNA-guided endonuclease introduces a double-stranded break, the target site in the chromosomal sequence is immediately followed by a protospacer adjacent motif (PAM), and repair of the double-stranded break by a DNA repair process leads to modification of the chromosomal sequence.

U.S. Application No. 15/456,204:

1.  A method for modifying a chromosomal sequence in a eukaryotic cell by integrating a donor sequence, the method comprising introducing into the eukaryotic cell: (i) a Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas) (CRISPR-Cas) type II protein linked to at least one nuclear localization signal (NLS) or a nucleic acid encoding the CRISPR-Cas type II protein linked to at least one NLS, wherein the CRISPR-Cas type II protein is a Cas9 protein, and the nucleic acid encoding the CRISPR-Cas type II protein is codon optimized for expression in the eukaryotic cell; (ii) a guide RNA or DNA encoding the guide RNA, wherein the guide RNA comprises a first region that is complementary to a target site in the chromosomal sequence that is immediately followed by a protospacer adjacent motif, and a second region that interacts with the CRISPR-Cas type II protein; and (iii) a donor polynucleotide comprising the donor sequence;
    wherein the guide RNA guides the CRISPR-Cas type II protein to the target site in the chromosomal sequence, the CRISPR-Cas type II protein introduces a double stranded break at the target site, and repair of the double-stranded break by a DNA repair process leads to integration or exchange of the donor sequence into the chromosomal sequence.

The relationship between patents and applications owned by Berkeley, the Broad, and Sigma are set forth in Figure 1 of the petition graphically as follows:

The Examiner (who is the same Examiner responsible for allowing Berkeley's patents), according to the petition, has provided no legal justification for refusing to acknowledge what Sigma contends is the precedential value of the decisions in the earlier interference.  Sigma's position is that if the Doudna et al. provisional applications did not provide sufficient support to find the Broad's claims obvious (in an interference context) they cannot support a determination of obviousness in ex parte patent prosecution involving Sigma's applications.  Sigma further alleges that the evidence adduced in its ex parte examination of the three identified pending applications is "even more extensive" than the record in the earlier Berkeley/Broad interference; here, Sigma asserts that it has provided "multiple declarations from prominent experts explaining in even greater detail why (a) UC's disclosure of CRISPR-Cas9 in a prokaryotic environment does not render obvious Sigma-Aldrich's CRISPR-Cas9 eukaryotic claims, and (b) UC's provisional applications (UC P1 and UC P2) do not enable or adequately describe use of CRISPR-Cas9 in eukaryotic cells."

According to the petition, the Examiner merely responds that their evidence is "unpersuasive" in refusing to recognize the allowability of their pending claims (in the latest Office Action, in the '911 application, Sigma asserts that this phrase or its equivalent was repeated "over 70 times").  (It is only fair to the Examiner to note that there was an in-person interview between Sigma's representatives and "the Examiner, her Supervisory Patent Examiner, two Interference Practice Specialists, and the Group Art Unit Director" that did not resolve the issue in Sigma's favor.)  Sigma-Aldrich argues that "[f]or the effective administration of justice, efficiencies of the USPTO and the parties, conservation of considerable valuable resources, and the public interest" the new interference should be declared (between Berkeley and Sigma in their petition; it is difficult to see the USPTO not including the Broad et al. patents in any such interference).  The alternative, according to the petition, would be appeal to the PTAB over the obviousness rejection and, if need be, further appeal to the Federal Circuit.

Confident of its position, Sigma contends that this would be contrary to the Director's recent pronouncements (albeit in a different context) regarding there being a "level playing field" for all applicants and other parties; this portion of the petition waxes wroth regarding the "palpable" unfairness to Sigma and that "[i]n today's highly charged political environment, certainly the Director and CAPJ are sensitive to criticism leveled at the Agency regarding issues of fairness and equity."  In addition, Sigma notes that it would be "grossly inefficient" for the USPTO to conduct the current interference between Berkeley and the Broad and then have to conduct a further interference between Sigma and either or both of the other parties.  Finally, the petition notes the public interest in resolving the priority and ownership disputes between the several parties to prevent inhibiting development of the technology due to uncertainties regarding licensing and freedom to operate issues.

Should the Director and/or Chief Judge grant Sigma its requested relief, it is likely that the current interference will be redeclared naming all three parties, the patents and applications currently in interference, and the Sigma-Aldrich applications (with their attendant priority claims).  The interfering subject matter has been set forth in alternate counts, corresponding either as claim 18 of the Broad's U.S. Patent No. 8,697,359 (dependent on claim 15), which taken together recites the following invention:

An engineered, programmable, non-naturally occurring Type II CRISPR-Cas system comprising a Cas9 protein and at least one guide RNA that targets and hybridizes to a target sequence of a DNA molecule in a eukaryotic cell, wherein the DNA molecule encodes and the eukaryotic cell expresses at least one gene product and the Cas9 protein cleaves the DNA molecules, whereby expression of the at least one gene product is altered; and, wherein the Cas9 protein and the guide RNA do not naturally occur together, wherein the guide RNAs comprise a guide sequence fused to a tracr sequence.

(where the underlined portion recites the relevant language from claim 18) and claim 156 of Berkeley's U.S. Patent Application No. 15/981,807:

A eukaryotic cell comprising a target DNA molecule and an engineered and/or non-naturally occurring Type II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-— CRISPR associated (Cas) (CRISPR-Cas) system comprising
    a) a Cas9 protein, or a nucleic acid comprising a nucleotide sequence encoding said Cas9 protein; and
    b) a single molecule DNA-targeting RNA, or a nucleic acid comprising a nucleotide sequence encoding said single molecule DNA-targeting RNA; wherein the single molecule DNA-targeting RNA comprises:
        i) a targeter-RNA that is capable of hybridizing with a target sequence in the target DNA molecule, and
        ii) an activator-RNA that is capable of hybridizing with the targeter-RNA to form a double-stranded RNA duplex of a protein- binding segment,
    wherein the activator-RNA and the targeter-RNA are covalently linked to one another with intervening nucleotides; and
    wherein the single molecule DNA-targeting RNA is capable of forming a complex with the Cas9 protein, thereby targeting the Cas9 protein to the target DNA molecule, whereby said system is capable of cleaving or editing the target DNA molecule or modulating transcription of at least one gene encoded by the target DNA molecule.

There is no time frame for the petition to be considered much less granted, but as Sigma notes, the latest Berkeley-Broad interference is in the earliest stage; the parties must submit their proposed motions to the Board by July 30th and a teleconference between the Board and the parties is scheduled for August 5th.  None of these dates is written in stone, of course, and the Director or the Board could postpone progress in the pending interference to consider Sigma's request.  That would be the logical course; whether it is the Office's course remains to be seen.